title: Protection against cyclophosphamide-induced alopecia and inhibition of mammary tumor growth by topical 1,25-dihydroxyvitamin D3 in mice.
abstract: Twenty-one-day-old BALB/c mice were shaved on the back to synchronize hair growth. On day 30 or 31, when at least 90% of mice exhibited hair regrowth in the shaved area, 1,25(OH)2D3 was applied topically to the shaved area daily for 5 days. On the 6th day, cyclophosphamide (Cytoxan, CTX) was injected i.p. to induce hair loss in the shaved area. Alopecia was induced in a dose-dependent manner by CTX treatment within 1 to 2 weeks. This effect was reduced significantly if mice were pre-treated with 1,25(OH)2D3, though only slight protection was observed in female mice. Interestingly, this 1,25(OH)2D3-mediated protection against hair loss was attenuated in male mice but became more significant in female mice when they were inoculated with the EMT-6 murine mammary tumor prior to treatment. More importantly, topical treatment with 1,25(OH)2D3 alone was able to inhibit EMT-6 tumor growth in both male and female BALB/c mice. Furthermore, 1,25(OH)2D3 pre-treatment also augmented the anti-tumor effect of CTX. Our results demonstrate that topical application of 1,25(OH)2D3 can protect against CTX-induced alopecia both in tumor-free and in tumor-bearing mice in a sex-dependent manner. Moreover, 1,25(OH)2D3 was shown, either alone or in combination with CTX, to inhibit tumor growth.
authors.affiliation: Department of Molecular Biology, The Cleveland Clinic Foundation, OH 44195, USA. cheng@cesmtp.ccf.org
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Baechle
authors.forename: T D
authors.initials: TD
authors.lastname: Nevins
authors.forename: S
authors.initials: S
authors.lastname: Oh
authors.forename: C
authors.initials: C
authors.lastname: Harmon
authors.forename: D W
authors.initials: DW
authors.lastname: Stacey
mesh_terms: D000287:Administration, Topical; D000505:Alopecia / Q000517:prevention & control*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D002117:Calcitriol / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000009:adverse effects*; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D002117:Calcitriol